Key information relevant to the recruitment process for the
overall study, such as dates of the recruitment period and locations

Patients were recruited from study sites in the United States and Argentina. There were 10 patients from Argentina.

Pre-Assignment Details

Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

No text entered.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Ranibizumab 0.5 mg

Patients received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Sham Injection/Ranibizumab 0.5 mg

Patients received a sham intravitreal injection monthly for 24 months. Patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Participant Flow for 3 periods

Period 1: Core Study

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

125

125

127

COMPLETED

98

100

86

NOT COMPLETED

27

25

41

Adverse Event

4

4

1

Death

6

4

4

Lost to Follow-up

5

5

10

Physician Decision

2

1

3

Subject Non-compliance

1

2

1

Subject Required Other Therapy

0

1

3

Subject's Decision

9

8

19

Period 2: Open-label Extension Through Month 48

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

89
[1]

79
[1]

77
[1]

COMPLETED

63

59

50

NOT COMPLETED

26

20

27

Adverse Event

0

0

2

Death

2

0

0

Lost to Follow-up

1

0

2

Physician's Decision

2

1

3

Subject's Decision

1

3

3

Sponsor’s Decision to Terminate Study

18

15

16

Subject Non-compliance

2

1

0

Subject Required Other Therapy

0

0

1

[1]

Not all participants who completed the core study entered the optional open-label extension.

Period 3: Open-label Extension Through Month 60

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

STARTED

89
[1]

79
[1]

77
[1]

COMPLETED

1

1

0

NOT COMPLETED

88

78

77

Adverse Event

0

0

2

Death

2

2

1

Lost to Follow-up

3

0

4

Physician's Decision

2

1

3

Subject's Decision

1

3

4

Sponsor’s Decision to Terminate Study

77

71

62

Subject Non-compliance

2

1

0

Subject Required Other Therapy

1

0

1

[1]

Not all participants who completed the core study entered the optional open-label extension.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

The Baseline Characteristics of the patients enrolled in the open-label extension phase (N=88, 83, 84 patients originally randomized to the ranibizumab 0.3 mg, ranibizumab 0.5 mg, and sham injection groups, respectively) were similar to the Baseline Characteristics of the patients enrolled in the core study.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 24 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 24 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months.

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24 [ Time Frame: Baseline to Month 24 ]

Measure Type

Primary

Measure Title

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

Time Frame

Baseline to Month 24

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward.

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

An adjustment was made for multiple treatment comparisons of the ranibizumab dose groups with the control group.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2 for Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Month 24

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

0.0002

Difference in percentage at Month 24 [4]

20.9

95% Confidence Interval

( 10.7 to 31.1 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

An adjustment was made for multiple treatment comparisons of the ranibizumab dose groups with the control group.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.

Time Frame

Baseline to Month 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed up to Month 36 using the last observation carried forward method. The Month 48 outcome measures are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

3. Secondary:

Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48 [ Time Frame: Months 24, 36, and 48 ]

Measure Type

Secondary

Measure Title

Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48

Measure Description

VA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the EDTRS chart.

Time Frame

Months 24, 36, and 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed up to Month 36 using the last observation carried forward method. The Month 48 outcome measures are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Statistical Analysis 1 for Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

<0.0001

Difference in percentage at Month 24 [4]

24.4

95% Confidence Interval

( 13.4 to 35.4 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2 for Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

<0.0001

Difference in percentage at Month 24 [4]

25.1

95% Confidence Interval

( 14.0 to 36.3 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

4. Secondary:

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48 [ Time Frame: Baseline to Month 48 ]

Measure Type

Secondary

Measure Title

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

Time Frame

Baseline to Month 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed up to Month 36 using the last observation carried forward method. The Month 48 outcome measures are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Measured Values

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection

Sham Injection/Ranibizumab 0.5 mg

Number of Participants Analyzed
[units: participants]

125

125

127

127

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48
[units: Percentage of patients]Number ( 95% Confidence Interval )

Month 24

97.6
( 94.9 to 100 )

97.6
( 94.9 to 100 )

89.8
( 84.5 to 95.0 )

NA
( NA to NA )
[1]

Month 36

99.2
( 97.6 to 100 )

97.6
( 94.9 to 100 )

NA
( NA to NA )
[1]

91.3
( 86.4 to 96.2 )

Month 48 (n=62,56,0,48)

100.0
( 94.2 to 100.0 )

100.0
( 93.6 to 100.0 )

NA
( NA to NA )
[1]

97.9
( 88.9 to 99.9 )

[1]

NA = not applicable, see reporting groups.

Statistical Analysis 1 for Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

0.0086

Difference in percentage at Month 24 [4]

8.2

95% Confidence Interval

( 2.4 to 14.1 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2 for Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

0.0126

Difference in percentage at Month 24 [4]

7.8

95% Confidence Interval

( 2.0 to 13.6 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

5. Secondary:

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline [ Time Frame: Baseline to Month 36 ]

Measure Type

Secondary

Measure Title

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.

Time Frame

Baseline to Month 36

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Subgroup of the intent-to-treat population: All randomized patients with focal edema at baseline, whether or not treatment was received. Missing data were imputed using the last observation carried forward method.

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. For 36-month outcome measures, data in this column represents efficacy data at Month 36.

Statistical Analysis 1 for Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

0.0005

Mean Difference (Final Values) [4]

9.7

95% Confidence Interval

( 4.3 to 15.1 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

Statistical Analysis 2 for Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

0.0011

Mean Difference (Final Values) [4]

8.2

95% Confidence Interval

( 3.3 to 13.0 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed up to Month 36 using the last observation carried forward method. The Month 48 outcome measures are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 24-month outcome measures, data in this column represents efficacy data at Month 24. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here. The statistical analysis was not performed at Month 48.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

7. Secondary:

Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36 [ Time Frame: Baseline to Month 36 ]

Measure Type

Secondary

Measure Title

Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward method.

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. For 36-month outcome measures, data in this column represents efficacy data at Month 36.

Statistical Analysis 1 for Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

0.1590

Difference in percentage at Month 24 [4]

-3.0

95% Confidence Interval

( -6.7 to 0.7 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2 for Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and 36

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

0.2721

Difference in percentage at Month 24 [4]

-2.5

95% Confidence Interval

( -6.5 to 1.4 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

8. Secondary:

Percentage of Patients With Resolution of Leakage at Month 24 [ Time Frame: Baseline to Month 24 ]

Measure Type

Secondary

Measure Title

Percentage of Patients With Resolution of Leakage at Month 24

Measure Description

Resolution of leakage was defined as total area of fluorescein leakage in the central, inner, and outer subfields of the 0 Disc Area. Leakage was assessed in fluorescein angiographic images by the central reading center.

Time Frame

Baseline to Month 24

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward method.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months.

Sham Injection

Patients randomized to this group received a sham intravitreal injection monthly for 24 months.

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2 for Percentage of Patients With Resolution of Leakage at Month 24

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

Cochran-Mantel-Haenszel

P Value [3]

<0.0001

Difference in percentage at Month 24 [4]

24.2

95% Confidence Interval

( 16.7 to 31.7 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

No text entered.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

The percentage for each group and the difference in percentage between groups were estimated using the weighted average of the observed percentages and the differences in observed percentages over the strata using the Cochran-Mantel-Haenszel weights.

9. Secondary:

Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36 [ Time Frame: Baseline to Month 36 ]

Measure Type

Secondary

Measure Title

Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Measure Description

The need for macular laser treatment was evaluated by the masked (evaluating) physician. Macular laser was administered per protocol-specified objective and subjective criteria starting at Month 3.

Time Frame

Baseline to Month 36

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed using the last observation carried forward method.

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. For 24-month outcome measures, data in this column represents efficacy data at Month 24.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. For 36-month outcome measures, data in this column represents efficacy data at Month 36.

Statistical Analysis 1 for Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Groups [1]

Ranibizumab 0.3 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

<0.0001

Mean Difference (Final Values) [4]

-1.0

95% Confidence Interval

( -1.4 to -0.7 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

Statistical Analysis 2 for Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36

Groups [1]

Ranibizumab 0.5 mg vs. Sham Injection

Method [2]

ANOVA

P Value [3]

<0.0001

Mean Difference (Final Values) [4]

-1.1

95% Confidence Interval

( -1.5 to -0.7 )

[1]

Additional details about the analysis, such as null hypothesis and power calculation:

The analysis summarized in this section is for the Month 24 time point, comparing the outcome for patients randomized to ranibizumab versus sham injections during the controlled treatment period. The statistical analysis for the Outcome Measure at Month 36 is not shown here.

[2]

Other relevant method information, such as adjustments or degrees of freedom:

Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:

To manage the type I error rate while testing multiple secondary efficacy endpoints for statistical significance, a type I error management plan was implemented. Secondary endpoints were prioritized and tested using a hierarchical testing procedure.

[4]

Other relevant estimation information:

No text entered.

10. Secondary:

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 36 and 48 [ Time Frame: Baseline to Month 48 ]

Measure Type

Secondary

Measure Title

Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 36 and 48

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

Time Frame

Baseline to Month 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. Missing data were imputed up to Month 36 using the last observation carried forward method. The Month 48 outcome measures are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 36-month outcome measures, data in this column represents efficacy data at Month 36. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Mean Change From Month 36 in Best Corrected Visual Acuity (BCVA) Score in the Study Eye at Month 48

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.

Time Frame

Month 36 to Month 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. The Month 48 data are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata. PRN) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

No statistical analysis provided for Mean Change From Month 36 in Best Corrected Visual Acuity (BCVA) Score in the Study Eye at Month 48

12. Secondary:

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48 [ Time Frame: Month 36 to Month 48 ]

Measure Type

Secondary

Measure Title

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48

Measure Description

BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

Time Frame

Month 36 to Month 48

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. The Month 48 data are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata. PRN) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Measured Values

Ranibizumab 0.3 mg

Ranibizumab 0.5 mg

Sham Injection/Ranibizumab 0.5 mg

Number of Participants Analyzed
[units: participants]

62

56

48

Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48
[units: Percentage of participants]Number ( 95% Confidence Interval )

93.5
( 84.3 to 98.2 )

96.4
( 87.7 to 99.6 )

100.0
( 92.6 to 100.0 )

No statistical analysis provided for Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in the Study Eye From Month 36 at Month 48

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Intent-to-treat population: All randomized patients, whether or not treatment was received. The Month 48 data are based on the observed data for patients enrolled in the open-label extension phase; missing data were not imputed.

Reporting Groups

Description

Ranibizumab 0.3 mg

Patients randomized to this group received ranibizumab 0.3 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Ranibizumab 0.5 mg

Patients randomized to this group received ranibizumab 0.5 mg monthly administered intravitreally for 36 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata. PRN) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.

Sham Injection/Ranibizumab 0.5 mg

Patients randomized to this group received a sham intravitreal injection monthly for 24 months. Although still masked, patients who had not discontinued treatment by Month 24 could choose to receive ranibizumab 0.5 mg monthly administered intravitreally for the subsequent 12 months. Patients who had not discontinued treatment by Month 36 could enter the open-label extension phase to receive ranibizumab 0.5 mg as needed (pro re nata [PRN]) for up to 24 additional months. For 48-month outcome measures, data in this column represents efficacy data at Month 48 for subjects enrolled in the open-label extension.